Griscelli syndrome
| Griscelli syndrome | |
|---|---|
| Classification and external resources | |
| OMIM | 214450 607624 609227 |
| DiseasesDB | 32776 34039 |
| eMedicine | derm/926 |
Griscelli syndrome is a rare autosomal recessive[1] disorder characterized by albinism (hypopigmentation) with immunodeficiency, that usually causes death by early childhood.
Types
Griscelli syndrome is a disorder of melanosome transport, and divided into several types[2]:866:
| OMIM | Name | Gene |
|---|---|---|
| 214450 | Griscelli syndrome type 1 (Elejalde syndrome) | MYO5A |
| 607624 | Griscelli syndrome type 2 (Partial albinism with immunodeficiency) | RAB27A |
| 609227 | Griscelli syndrome type 3 | MLPH |
Presentation
Griscelli syndrome is defined by the characteristic hypopigmentation, with frequent pyogenic infection, hepatosplenomegaly, neutropenia, thrombocytopenia, and immunodeficiency. Very often there is also impaired natural killer cell activity, absent delayed-type hypersensitivity and a poor cell proliferation response to antigenic challenge. This may be caused by the loss of three different genes, each of which has different additional effects, resulting in three types of syndrome. Its Inheritance is autosomal recessive.
Examination of the hair in this syndrome may be useful. Under light microscopy, these hairs exhibit bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, the hairs appear monotonously white.[3]
Pathophysiology
In melanocytes, melanosomes (vesicles containing the pigment melanin) are transported on microtubules. They are then bound by Rab27A which recruits Slac2-a and myosin Va. This complex then transfers the melanosomes from the microtubules to actin filaments. This transfer is necessary for the transport of melanosomes from the perinuclear area to the cell periphery. The loss of any one of these proteins interrupts melanosome transport and results in the hypopigmentation.
However, these three proteins do not work together in other cells and Rab27A effectors may be 'mix and match' For example the knockout of Rab27 causes the hypopigmentation but also immunodeficiency due to deficiencies in cytotoxic killing activity in cytotoxic T cells (something that also depends on vesicle transport). While, the knockout of myosin Va does not cause immunodeficiency, but it does cause neural defects. Though some neural problems (i.e. brain damage) can be seen in Rab27A deficient children, this is thought to be a secondary effect of the immune problems, and not directly due to the lack of Rab27A.
Eponym
It is named after Claude Griscelli, professor of pediatry at Hôpital des Enfants-Malades in Paris (France).[4][5]
References
- ↑ Griscelli C, Durandy A, Guy-Grand D, Daguillard F, Herzog C, Prunieras M (1978). "A syndrome associating partial albinism and immunodeficiency". Am. J. Med. 65 (4): 691–702. doi:10.1016/0002-9343(78)90858-6. PMID 707528.
- ↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
- ↑ Valente NY, Machado MC, Boggio P, Alves AC, Bergonse FN, Casella E, Vasconcelos DM, Grumach AS, de Oliveira ZN (2006) Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes. Clinics (Sao Paulo) 61(4):327-332.
- ↑ synd/3872 at Who Named It?
- ↑ Griscelli C, Prunieras M (1978). "Pigment dilution and immunodeficiency: a new syndrome". Int. J. Dermatol. 17 (10): 788–91. doi:10.1111/j.1365-4362.1978.tb05980.x. PMID 730432.
External links
- Griscelli syndrome type 1 at NIH's Office of Rare Diseases OMIM: 214450
- Griscelli syndrome type 2 at NIH's Office of Rare Diseases OMIM: 607624
- Griscelli syndrome type 3 at NIH's Office of Rare Diseases OMIM: 609227
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